WO2012060792A1 - Compositions pharmaceutiques comprenant au minimum 6% en poids de délitants - Google Patents

Compositions pharmaceutiques comprenant au minimum 6% en poids de délitants Download PDF

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Publication number
WO2012060792A1
WO2012060792A1 PCT/TR2011/000257 TR2011000257W WO2012060792A1 WO 2012060792 A1 WO2012060792 A1 WO 2012060792A1 TR 2011000257 W TR2011000257 W TR 2011000257W WO 2012060792 A1 WO2012060792 A1 WO 2012060792A1
Authority
WO
WIPO (PCT)
Prior art keywords
formulation
formulation according
pharmaceutical composition
disintegrant
cefdinir
Prior art date
Application number
PCT/TR2011/000257
Other languages
English (en)
Inventor
Mahmut Bilgic
Original Assignee
Mahmut Bilgic
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Mahmut Bilgic filed Critical Mahmut Bilgic
Publication of WO2012060792A1 publication Critical patent/WO2012060792A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
    • A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A61K31/429—Thiazoles condensed with heterocyclic ring systems
    • A61K31/43—Compounds containing 4-thia-1-azabicyclo [3.2.0] heptane ring systems, i.e. compounds containing a ring system of the formula, e.g. penicillins, penems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/542—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/545—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine
    • A61K31/546—Compounds containing 5-thia-1-azabicyclo [4.2.0] octane ring systems, i.e. compounds containing a ring system of the formula:, e.g. cephalosporins, cefaclor, or cephalexine containing further heterocyclic rings, e.g. cephalothin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/4841—Filling excipients; Inactive ingredients
    • A61K9/4866—Organic macromolecular compounds

Definitions

  • the present invention relates to pharmaceutical compositions comprising cefdinir as the active agent and a production method that shall be used for preparation of these compositions.
  • Cefdinir the chemical name of which is (6R,7R)-7-[[(2Z)-(2-amino-4- thiazolyl)(hydroxyimino) acetyl]amino]-3-ethynyl-8-oxo-5-thia-l-azabicyclo[4.2.0]oct-2-ene- 2-carboxylic acid, was first disclosed in the patent numbered BE897864.
  • the chemical structure of cefdinir is seen in Formula 1. This third generation cephalosporin molecule is indicated for the treatment of infections caused by gram positive and gram negative bacteria.
  • cefdinir Physically appearing as a white powder, cefdinir has quite low solubility in common organic solvents such as methanol, ethanol, acetonitrile and in water. Due to this property, some problems are observed while developing formulations comprising this molecule.
  • cefdinir formulations having desired water solubility in order to provide effective and easy treatment for patients receiving cefdinir treatment.
  • the present invention relates to cefdinir formulations. Surprisingly, it was seen that the dosage forms prepared with the pharmaceutical composition obtained in the case that the amount of disintegrant used in the formulation comprising cefdinir is minimum 6%, preferably in the range of 6%-15%, more preferably in the range of 8%-13% by weight display better dissolution.
  • the subject of the present invention is cefdinir formulations comprising minimum 6%, preferably in the range of 6% - 15%, more preferably in the range of 8% - 13% of disintegrant by weight in proportion to total weight of the unit dose.
  • Said formulations can be formulated in a pharmaceutically acceptable dosage form, for instance in solid oral dosage forms such as tablet, film-coated tablet, capsule, prolonged- release tablet, modified-released tablet, effervescent tablet, orodispersible tablet, sachet, dry powder to form suspension; and/or liquid dosage forms such as suspension.
  • the formulation is in the form of tablet, more preferably in the form of film-coated tablet.
  • Cefdinir used in the formulations prepared according to the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free form and/or the combination thereof.
  • the disintegrant that can be used in the cefdinir formulation of the present invention can be selected from a group comprising carboxymethyl cellulose calcium, carboxymethyl cellulose sodium, microcrystalline cellulose, silicon dioxide, croscarmellose sodium, crospovidone, hydroxypropyl cellulose, methyl cellulose, povidone, magnesium aluminum silicate, starch or combinations thereof.
  • carboxymethyl cellulose sodium or carboxymethyl cellulose calcium or a disintegrant composition composed of the combination thereof is used. More preferably, carboxymethyl cellulose calcium is used.
  • the present invention relates to cefdinir formulations comprising minimum 6% of carboxymethyl cellulose calcium and tablet forms comprising this formulation.
  • the pharmaceutical composition of the present invention comprises at least one pharmaceutically acceptable excipient along with cefdinir and the disintegrant.
  • the excipients comprised in said composition can be selected from a group comprising diluents, humectants, binders, lubricants, sweeteners and/or glidant.
  • the binder that can be used in the cefdinir formulation of the present invention can be selected from a group comprising ethyl cellulose, gelatin, hydroxyethyl cellulose, hydroxymethyl cellulose, hydroxypropyl cellulose, hypromellose, magnesium aluminum silicate, methylcellulose, polyvinylpyrrolidone.
  • Polyvinylpyrrolidone is preferably used in the pharmaceutical composition of the invention.
  • the lubricant that can be used in the cefdinir formulation of the present invention can be selected from a group comprising calcium stearate, magnesium stearate, polyethylene glycol, PEG 6000, polyvinyl alcohol, potassium benzoate, sodium benzoate.
  • Magnesium stearate is preferably used in the present invention.
  • the humectant that can be used in the cefdinir formulation of the present invention can be selected from a group comprising anhydrous sodium sulphate, silica gel and potassium carbonate.
  • the diluent that can be used in the cefdinir formulation of the present invention can be selected from a group comprising calcium carbonate, calcium sulphate, dibasic calcium phosphate, tribasic calcium phosphate, calcium sulphate, microcrystalline cellulose, lactose, magnesium carbonate, magnesium oxide, maltodextrin, maltose, mannitol, sodium chloride, sorbitol, starch, xylitol or combinations thereof.
  • the sweetener that can be used in the cefdinir formulation of the present invention can be selected from a group comprising acesulfame, aspartame, dextrose, fructose, glucose, lactitol, maltitol, maltose, sorbitol, saccharine, saccharine sodium, sodium cyclamate, sucralose, sodium chloride, potassium chloride, sucrose, xylitol or combinations thereof.
  • the glidant that can be used in the cefdinir formulation of the present invention can be selected from a group comprising magnesium silicate, silicon dioxide, starch, talc, tribasic calcium phosphate or the combination thereof.
  • silicon dioxide is used as glidant in the formulation of the invention.
  • cefdinir formulation to be prepared according to the process of the invention can comprise 1 -4000 mg of cefdinir or its pharmaceutically acceptable salts, hydrates, solvates or the combination thereof in an equivalent amount.
  • the cefdinir formulation of the present invention can comprise 10-90 %, preferably 40-80 % of cefdinir or its pharmaceutically acceptable solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms and 0.1-10 % of binder, 0.1-10% of lubricant, 0-5% of sweetener, 0.1-30 % of diluent, 6-15 % of disintegrant, 0-10% of humectant, 0,1-5% of glidant in proportion to total weight of the unit dose amount.
  • a second active agent can be used in the cefdinir formulation of the present invention.
  • the second active agent can be selected from cephalosporins, beta-lactamases though clavulanic acid or its derivatives is preferably used.
  • the clavulanic acid that can be optionally used in the pharmaceutical composition of the present invention can be in the form of its solvates, hydrates, enantiomers, racemates, organic salts, inorganic salts, polymorphs, crystalline and amorphous forms or free form and/or the combination thereof.
  • potassium clavulanate is used in the present invention.
  • the pharmaceutical composition of the present invention can comprise clavulanic acid in the range of 50-500 mg or its pharmaceutically acceptable salts, hydrates, solvates or the combination thereof in an equivalent amount.
  • Clavulanic acid and its derivatives are extremely susceptible to moisture.
  • potassium clavulanate in the pharmaceutical composition of the present invention is preferably used with a humectant in the ratio of 1 : 1.
  • colloidal silica for instance colloidal silica anhydrous, for example Aerosil® 200, magnesium trisilicate, cellulose powder, Cabosil®, magnesium oxide, calcium silicate, Syloid®, starch, microcrystalline cellulose, talc can be used as the humectant.
  • potassium clavulanate is preferably used with syloid in the ratio of 1 :1.
  • the pharmaceutical composition of the present invention can comprise 5-90%, preferably 10- 80% of clavulanic acid in proportion to total weight of unit dose amount or pharmaceutically acceptable salts, hydrates, solvates or the combination thereof in an equivalent amount.
  • the present invention relates to processes that can be used for preparation of formulations comprising pharmaceutically acceptable excipients in addition to cefdinir as active agent.
  • the process of the present invention comprises granulation of the active agent cefdinir by conventional wet and/or dry granulation methods; or powdering cefdinir and the other excipients after mixing them by dry blending method and optionally compressing tablets or filling the mixture into sachets or capsules, if required, a second active agent is added to the formulation and is formulated by using the methods as specified above.
  • composition prepared according to said invention is used in the treatment of diseases related with infections caused by gram negative and gram positive bacteria.
  • EXAMPLE 1 Formulation and process for preparation of film-coated tablet comprising cefdinir.
  • Cefdinir is mixed with a part of the diluent, a part of the disintegrant and granulated with the granulation solution composed of aqueous solution of the binder. Obtained granules are dried and mixed with the binder, rest of the disintegrant, glidant and the other excipients. Then the lubricant is added and mixed again. Obtained mixture is loaded to the tablet compression machine and then the tablets are coated with an appropriate coating agent.
  • Example 2 Formulation and process for preparation of capsule comprising cefdinir and potassium clavulanate.
  • Cefdinir is mixed with a part of the diluent, a part of the disintegrant and is granulated with the granulation solution composed of aqueous solution of the binder. Obtained granules are dried and potassium clavulanate, diluent and rest of the disintegrant, glidant and the other excipients are added and mixed. Then lubricant is added and mixed again. Obtained mixture is loaded to the tablet compression machine and then the tablets are coated with an appropriate coating agent.

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Preparation (AREA)
  • Cephalosporin Compounds (AREA)

Abstract

L'invention concerne des compositions pharmaceutiques comprenant un principe actif de type cefdinir ainsi qu'un procédé de production à utiliser pour la préparation de ces compositions.
PCT/TR2011/000257 2010-11-05 2011-11-03 Compositions pharmaceutiques comprenant au minimum 6% en poids de délitants WO2012060792A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
TR2010/09165A TR201009165A2 (tr) 2010-11-05 2010-11-05 Sefdinir içeren tabletler
TR2010/9165 2010-11-05

Publications (1)

Publication Number Publication Date
WO2012060792A1 true WO2012060792A1 (fr) 2012-05-10

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/TR2011/000257 WO2012060792A1 (fr) 2010-11-05 2011-11-03 Compositions pharmaceutiques comprenant au minimum 6% en poids de délitants

Country Status (2)

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TR (1) TR201009165A2 (fr)
WO (1) WO2012060792A1 (fr)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021058047A1 (fr) 2019-09-25 2021-04-01 Schaeffler Technologies AG & Co. KG Chaîne cinématique hybride

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE897864A (fr) 1982-09-30 1984-03-29 Fujisawa Pharmaceutical Co Procede de production de composes de 3-vinyl-3-cephem 7-substitues et nouveaux produits ainsi obtenus
WO2007125541A1 (fr) * 2006-05-01 2007-11-08 Lupin Limited Compositions pharmaceutiques de cefdinir
EP2366379A1 (fr) * 2010-02-25 2011-09-21 Sanovel Ilac Sanayi ve Ticaret A.S. Forme de cefdinir avec taux de dissolution amélioré

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE897864A (fr) 1982-09-30 1984-03-29 Fujisawa Pharmaceutical Co Procede de production de composes de 3-vinyl-3-cephem 7-substitues et nouveaux produits ainsi obtenus
WO2007125541A1 (fr) * 2006-05-01 2007-11-08 Lupin Limited Compositions pharmaceutiques de cefdinir
EP2366379A1 (fr) * 2010-02-25 2011-09-21 Sanovel Ilac Sanayi ve Ticaret A.S. Forme de cefdinir avec taux de dissolution amélioré

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
ZHANG R ET AL: "Effervescent cefdinir prepn and its preparation process consists cefdinir disintegrating agent including acid and alkali and other components which are stuffing, adhesive, moistener, lubricant, sweetener and aromatic", WPI / THOMSON,, 14 December 2005 (2005-12-14), XP002620814 *

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021058047A1 (fr) 2019-09-25 2021-04-01 Schaeffler Technologies AG & Co. KG Chaîne cinématique hybride

Also Published As

Publication number Publication date
TR201009165A2 (tr) 2012-05-21

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